Head Squamous Cell Carcinoma Research Articles

Tumor Hyperprogression in Squamous Cell Carcinomas of Head and Neck after Immunotherapy: Our Perspective

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. Although there have been some advances in multimodality therapy, the overall 5-year survival rate remains poor approximately at 40%-50%. Currently, Immune Checkpoint Inhibitor (ICI) based Immunotherapies are being evaluated as an alternate treatment modality for recurrent/metastatic HNSCCs in clinical trials.

Immunohistochemical Expression of P63 and P40 in Squamous Cell Carcinoma of Head and Neck

Background: Squamous cell carcinoma (SCC) in head and neck region has a high worldwide prevalence. Increased accuracy in diagnosis is achieved by immunohistochemical markers. Objectives: To evaluate the immunohistochemical expression of p63 and p40 in SCC and correlate with histological grades to determine p40 as a better potential diagnostic immunohistochemical marker for SCC. Methods: Descriptive cross-sectional study was conducted on eighty-three cases of SCC of head and neck from March 2020 to February,2022 at Pathology Department, KEMU, Lahore. Data including age, sex, risk factors and tumor site was collected. SCC grading was done on H&E stained tissue sections. Staining with p63 and p40 was performed and independently scored for percentage of tumor cells stained and intensity of nuclear staining. The results were compared using H-scores in all grades of SCC. Data was entered in Statistical Package for Social Sciences(SPSS-26). Quantitative variables like age were presented as mean ±SD. Qualitative variables as frequency and percentages. Correlation of two groups was done by applying Chi-square test. P value ≤0.05 was taken as significant. Results: SCC was graded according to the W.H.O. grading system. All cases stained positive for p63 and p40. Strong nuclear staining by p40 was observed in 65.02% cases versus 42.17% by p63. The mean tumor area stained by p40 was greater than p63 (90.35% vs 75.5%) in all cases. A significant higher mean H-score for p40 (9.69±2.86) versus p63 (7.05±3.12) was observed as indicated by significant P-value. The mean H-score of p40 immunoreactivity was 10.11 and p63 was 6.00 in poorly differentiated SCC. Males comprised 74.70% cases whereas females 25.30% only. SCC in oral cavity was (96.39%) followed by oropharynx and larynx. Conclusion: P40 immunohistochemical marker was better compared to P63 for the diagnosis of SCC particularly in poorly differentiated SCC.

Conventional chemoradiation versus accelerated chemoradiation: A prospective study in oropharyngeal cancer

Background: Squamous-cell carcinoma of the head and neck is predominantly a loco regional disease, and the primary treatment methods are surgery and radiotherapy. For patients with locally-regionally advanced oropharyngeal cancer, concurrent chemoradiotherapy is the standard treatment. Material and Method: The aim and objectives of study were a) to compare locoregional response in two arms, b) to compare acute and chronic treatment-related toxicities in the two arms, and c) to compare the quality of life. The study was conducted between August 2014 and April 2016, with 86 patients of histologically proven squamous-cell carcinoma of oropharynx. This is a prospective trial to assess the suitability of five versus six weekly radiotherapy fractions, along with concurrent cisplatin, given to the same total dose, in all stages of oropharyngeal cancer patients. Result: Patients were randomized into two arms: conventional arm (Arm A), which received 5 fractions per week RT -70GY/7 weeks/35#, and accelerated arm (Arm B), which received 6 fractions per week RT -70GY/6 weeks/35. Locoregional squamous-cell carcinoma improved significantly in the accelerated fractionation group compared with that in the conventional RT group. Conclusion: Accelerated RT enhances improvement of locoregional control in the squamous-cell carcinoma of head and neck region, with reduction in overall treatment time and concurrent chemotherapy. Locoregional control of carcinoma improved significantly in the accelerated fractionation group compared with that in the conventional RT group.

854MO Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Final analysis of randomized phase III GORTEC 2017-01 REACH trial

854MO Avelumab-cetuximab-radiotherapy (RT) versus standards of care in patients with locally advanced squamous cell carcinoma of head and neck (LA-SCCHN): Final analysis of randomized phase III GORTEC 2017-01 REACH trial

The Frequency and the Significance of TNF-α+CD19+ B-cell Population in Lymph Nodes of Patients with Squamous Cell Carcinoma of Head and Neck

The Frequency and the Significance of TNF-α+CD19+ B-cell Population in Lymph Nodes of Patients with Squamous Cell Carcinoma of Head and Neck

Walking one hour per day and the derived neutrophil-to-lymphocyte ratio are associated with outcome in palliative second-line immunotherapy for patients with recurrent and/or metastatic squamous cell carcinoma of head and neck

ObjectivesTo determine whether routinary walking activity and the derived neutrophil-to-lymphocyte ratio are associated with outcomes in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck. MethodsThis multicenter retrospective cohort study included 64 patients diagnosed with recurrent and/or metastatic squamous cell carcinoma of head and neck and treated with immunotherapy (Programmed Death-1 and Programmed Death-ligand-1 proteins inhibitors) at two tertiary centers. We compared a group that performed uninterrupted physical activity for 1 h per day and controls who performed no activity. The derived neutrophil-to-lymphocyte ratio was calculated as follows: [neutrophils / (leukocytes – neutrophils)]. Progression-free survival and overall survival were evaluated. ResultsWe included 28 (44%) and 36 (56%) patients in the activity and non-activity groups, respectively. Patient characteristics, treatment details, and tumor Programmed Death-ligand-1 expression were not associated with either progression-free survival or overall survival. Physical activity was an independent beneficial factor for progression-free survival (p < 0.001) and overall survival (p < 0.001). By contrast, a derived neutrophil-to-lymphocyte ratio <3.5 was an independent beneficial factor for overall survival (p = 0.013), but not for progression-free survival (p = 0.328). ConclusionsWalking one hour per day and having a high proportion of lymphocytes to neutrophiles (expressed as a low derived neutrophil-to-lymphocyte ratio) independently predict a better prognosis in patients with recurrent and/or metastatic squamous cell carcinoma of head and neck treated with immunotherapy. Level of evidenceIII.

Weekly paclitaxel, carboplatin and cetuximab (PCC) combination followed by nivolumab in platinum-sensitive recurrent and /or metastatic squamous cell carcinoma of head and neck: a retrospective analysis from two institutions in India

Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 &amp; PFS-2), overall survival (OS), and safety were evaluated. Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.

Tumor thickness as a novel risk factor for lymph node metastasis by superficial squamous cell carcinoma of head and neck.

Narrow-band imaging combined with magnified endoscopy has enabled the detection of superficial squamous cell carcinoma of the head and neck (SSCCHN) that has been resected with minimally invasive treatment, preserving vocalization and swallowing functions. However, risk factors of lymph node metastasis (LNM) must be identified, as some patients with LNM have a poor prognosis. From an initial 599 patients with 700 lesions who underwent trans-oral surgery in 27 Japanese hospitals (a nationwide registration survey), we enrolled 541 patients with 633 SSCCHNs, as indicated by central pathological diagnoses. All pathological specimens for each patient were examined using 20 pathological factors that are thought to affect the LNM of SSCCHN. In all, 24 (4.4%) of the 568 SSCCHNs exhibited LNM, and all 24 had at least one solitary nest of epithelial neoplastic cells present in the stroma, clearly separated from the intraepithelial carcinoma. Multivariate analysis also showed that tumor thickness (p = 0.0132, RR: 7.85, 95% confidence interval [CI]: 1.54-40.02), and an INFc pattern classified as infiltrating growth (INF) with unclear boundaries between tumor and non-tumor tissues (p = 0.0003, RR: 14.47, 3.46-60.46), and tumor budding (p = 0.0019, RR: 4.35, CI: 1.72-11.01) were significantly associated with LNM. Solitary nests may be indicative of LNM. In addition, tumor thickness was revealed to be a risk factor for LNM in SSCCHNs using pT factors that do not include an invasion depth element because of the anatomical absence of the muscularis mucosae.

Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials

Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials

Assessing Patient Risk, Benefit, and Outcomes in Drug Development: Insights From Afatinib Clinical Trials Across Diverse Cancer Indications

PurposeIn 2013, afatinib was approved for non–small-cell lung cancer with subsequent indication expansion. We investigated published afatinib clinical trials to assess risk and benefit profiles for the drug in its approved indication of non–small-cell lung cancer as well as in off-label uses. Previous literature demonstrates excessive patient burden and limited benefit as afatinib has spread into more indications. A trial analysis is needed to establish efficacy and risk. MethodsIn this investigation, we screened literature databases and clinical trial registries for trials of afatinib as monotherapy or in combination interventions for cancer treatment. We extracted participant demographics, adverse event characteristics, as well as clinical and surrogate endpoints for each trial. Studies were deemed positive, negative, or indeterminate based on their achieving of primary endpoints as well as their safety. ResultsOur search yielded 2444 articles; we excluded 2352 articles for a final inclusion of 92 trials of 8859 patients. Our sample had 49 (53%) positive trials, 27 (29%) negative trials, and 16 (17%) indeterminate trials. The most common off-label indications for afatinib were breast cancer and squamous cell carcinoma of head and neck. The median OS for all trials was 8.4 months, median PFS 3.4 months, and the total ORR was 29.6%. Our study found that trials performed in disease states beyond the initial indications were largely negative with little patient benefit. The adverse events within our trial sample appear to be in line with expectations for toxicity. ImplicationsThese results are consistent with other studies that present similar findings, such as in Carlisle et al which indicate limited efficacy in nonapproved indications. Future trials should keep this potential evidence and patient burden in mind before initiation of those trials. This study contributes to the understanding of afatinib's risk-benefit profile across many clinical applications.

Comparison of Outcome of Concurrent Chemoradiotherapy and Sequential Chemoradiotherapy in Locally Advanced, Inoperable Squamous Cell Carcinoma of Head and Neck Region

Background: Head and neck cancer is prevalent in Bangladesh, with a majority of patients presenting with locally advanced, inoperable disease. This study aimed to compare the effectiveness and accessibility of concurrent and sequential (CCRT with RT) chemoradiotherapy in treating this condition, addressing a debate among oncologists. Materials and Methods: A quasi-experimental study at Rajshahi Medical College Hospital (June 2019 - May 2020) involved 60 inoperable head and neck cancer patients, comparing concurrent chemoradiotherapy with Cisplatin and sequential chemoradiotherapy with Paclitaxel and Cisplatin, monitoring treatment response and toxicities. Results: The mean age was 56.1 (±9.5) years in Arm-A and 56.9 (±9.4) years in Arm-B. The primary endpoint was loco-regional control and early toxicities. In the final response, 14 weeks after the completion of treatment, the overall loco-regional control rate was 86.67% and 76.67% in Arm-A and Arm-B, respectively. Severe toxicities include grade 3 reaction only and happened 18(58%) vs 13(42%) in Arm-A and Arm-B, respectively. Among severe toxicities, mucositis and skin reaction were higher in the concurrent Arm and anemia and neutropenia were higher in the sequential Arm. However, there was no actual difference in the two treatment modalities (p=&gt;0.05). The overall treatment time was short in concurrent chemoradiotherapy (49 vs 133 days) and lower treatment cost as well, which was statistically significant (p=&lt;0.0001). Conclusion: concurrent chemoradiotherapy proves cost-effective and accessible, demonstrating outcomes similar to sequential chemoradiotherapy. It stands as a viable treatment choice for locally advanced, inoperable head and neck squamous cell carcinoma.

Sentinel lymph node biopsy versus observation in high risk cutaneous squamous cell carcinoma of head and neck: a propensity score matching analysis.

Sentinel lymph node biopsy (SLNB) has gained considerable attention in the management of head and neck cutaneous squamous cell carcinoma (HNcSCC). The aim of this study was to compare the oncologic outcomes between observation and SLNB in cN0 high-risk HNcSCC patients. We retrospectively enrolled patients from the SEER database and evaluated the impact of observation versus SLNB on disease-specific survival (DSS) and overall survival (OS) using a Propensity Score Matching (PSM) analysis. A total of 9804 patients were included, with 1169 cases treated by SLNB. Successful retrieval of the sentinel lymph node was achieved in 1130 procedures. After PSM and subsequent multivariate analysis, SLNB was found to be an independent predictor for improved DSS, with a hazard ratio of 0.70 (95% confidence interval: 0.56-0.86). In patients presenting with two or three high-risk factors, SLNB was associated with better DSS (p = 0.021 and p = 0.044), but similar OS (p = 0.506 and p = 0.801) when compared to observation. However, in patients exhibiting four high-risk factors, SLNB demonstrated significantly improved DSS (p = 0.040) and OS (p = 0.028) compared to observation. Our findings suggest that SLNB is a highly feasible technique in HNcSCC and provides significant survival benefits. It is strongly recommended in patients with two or more high-risk factors, as it can help guide treatment decisions and improve patient outcomes.

Concurrent chemoradiation with low-dose and long-duration weekly infusion of gemcitabine in unresectable squamous cell carcinoma of head and neck (SCCHN).

Concurrent chemoradiotherapy now represents the standard of care in locally advanced unresectable squamous cell carcinoma of the head and neck, and the administration of cisplatin in triweekly or weekly schedules is the most commonly used chemotherapeutic agent. However, the chemotherapeutic agent and its scheduling with radiation is still an area of investigation with safer toxicity profile and better response rates. Gemcitabine is a potent radiosensitizer, and non-cytotoxic concentration results in decreased systemic toxicity while maintaining radiosensitization properties. Furthermore, data are emerging for low-dose and long-duration infusion where this strategy is found to be effective and a safe alternative to standard brief infusion. Based on these two strategies, that is, non-cytotoxic concentration with long duration, we have explored the unique possibility of further lowering the toxicity profile without compromising the efficacy. Eligible patients of locally advanced unresectable squamous cell carcinoma of the head and neck underwent radiation treatment with concurrent gemcitabine. A total dose of 70 Gy in 35 fractions over a period of seven weeks with conventional fractionation schedule was delivered with cord off after 44 Gy. Concurrent gemcitabine was administered intravenously for over two hours once a week, 1-2 h before radiation and for seven consecutive weeks at 50 mg/m2. Fifty-two patients was enrolled in this study, out of which 41 completed the treatment. Fifty-nine percent completed treatment within seven weeks. Sixty-four percent were found to have received more than five cycles. Mean follow-up of patients was found to be 4.9 months. Sixty-eight percent had complete response. Stage III patients achieved more complete response compared to stage IV. There was no site-wise difference in achieving complete response. Patients who have received less than five chemo cycles or completed the treatment in more than seven weeks had less complete response. Sixty-one percent had severe mucositis while 39% developed mild/moderate mucositis. Considering skin toxicity, 80% were found to have mild/moderate skin toxicity, while only 20% suffered from severe grades of skin toxicity. Gemcitabine in low-dose and long-duration infusion is a potent radiosensitizer with safer hematological toxicity and manageable local toxicities.

Abstract 4553: DXC004A, a novel EGFR antibody-tubulysin analog conjugate demonstrated potential to broaden therapeutic opportunities for non-small cell lung cancer

Abstract EGFR is a member of the epidermal growth factor receptor (HER) family, and the over-expression of EGFR plays an important role in the growth and progression of various tumors, including non-small cell lung cancer. Monoclonal EGFR antibodies, such as cetuximab and panitumumab, have proven efficacy in various types of cancer. However, treatment with the anti-EGFR agents can be associated with toxicities of the skin, nails, hair, and eyes. Nimotuzumab (Nimo) is the first humanized monoclonal antibody targeting EGFR and has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. In contrast to cetuximab, Nimotuzumab is distinguished by achieving higher or similar complete remission rate (CRR) or overall remission rate (ORR) of the primary tumor in clinical applications but much less toxicity, resulting in a better safety profile, which has been attributed to its about 10-fold lower affinity. Paclitaxel combined with cisplatin is the first-line chemotherapy regimen for non-small cell lung cancer. A phase 2 clinical trial has confirmed that Nimotuzumab combined with concurrent chemoradiation therapy (radiation concurrent with docetaxel and cisplatin, CCRT) was well tolerated for locally advanced squamous cell lung cancer. However, the combination strategy of Nimo-CCRT has only demonstrated similar OS and PFS to those in the CCRT group. DXC004A is an ADC drug targeting EGFR, in which a Nimotuzumab derivative and a Tubulysin B analog is conjugated by a functional linker. DXC004A is in phase I clinical trial and has demonstrated clinical activity in advanced non-small cell lung cancers and good tolerability. In vitro and in vivo results had confirmed that DXC004A monotherapy had better anti-tumor activity than the combination of Nimotuzumab and Tubulysin analog in HCC827 cell lines with high EGFR expression. Meanwhile, a single injection of low-dose DXC004 (2.5 mg/kg) in HCC827 xenograft model showed very good durable anti-tumor effect. Moreover, the combination of DXC004A with Cisplatin exhibited significantly better activities than that of Nimo-CCRT combination, DXC004A or cisplatin alone, in vitro and in vivo, which might solve the predicament of poor efficacy of Nimo-CCRT combination therapy. This synergy results suggested that DXC004A plus cisplatin would possibly be a new adjuvant therapy for non-small cell lung cancer in further clinical studies. Citation Format: Xiaobo Cai, Min Cao, Huihui Guo, Qingliang Yang, Yongxiang Chen, Xiangfei Kong, Yong Du, Zhicang Ye, Zhixiang Guo, Lingli Zhang, Lu Bai, Junxiang Jia, Yunxia Zheng, Wei Zheng, Jun Zheng, Wenjun Li, Yuanyuan Huang, Zhongliang Fan, Binbin Chen, Meng Dai, Robert Y. Zhao. DXC004A, a novel EGFR antibody-tubulysin analog conjugate demonstrated potential to broaden therapeutic opportunities for non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4553.

A Pilot Clinical Trial of Sodium Thiosulfate (STS) for Prevention of Ototoxicity in Patients with Locally Advanced Squamous Cell Carcinoma of Head and Neck (SCCHN) Undergoing Concurrent Chemoradiation with Cisplatin

A Pilot Clinical Trial of Sodium Thiosulfate (STS) for Prevention of Ototoxicity in Patients with Locally Advanced Squamous Cell Carcinoma of Head and Neck (SCCHN) Undergoing Concurrent Chemoradiation with Cisplatin

A Prospective Comparative Study of Sensorineural Hearing Loss in Patients of Head and Neck Cancers Treated with 2-D RT vs 3-D CRT

Background: SNHL is disabling for the patient, since it has a chronic and often Progressive natural history. sensorineural hearing loss is irreversible, whereas conductive hearing loss (as often found after radiotherapy) is mainly reversible. Material and Methods: This prospective randomized study was conducted in Department of Radiation Oncology, S P medical college Bikaner, Rajasthan. The study was done from November 2020 to October 2021. After taking informed consent total of 50 patients of biopsy proven squamous cell carcinoma of head and neck region randomly distributed among Group A who received 2D RT (2Gy/Fr in 30 to 35 fractions for 6 to 7 weeks) and Group B who received 3D CRT (2Gy/fr) in 30 to 35 fractions for 6 to 7 weeks).Result: After completion of treatment SNHL assessment was done in patients treated with conventional and conformal radiotherapy which was for speech frequency 15% and 8 % respectively and for high frequency was 45% and 28% respectively. After 3 month of completion SNHL for speech frequency 27.5% and 12% respectively and for high frequency was 62.5% and 32% respectively. Conclusion: High-frequency hearing loss can have a significant impact on quality of life because it affects speech discrimination, conventional radiotherapy experienced greater hearing loss as compared of conformal.

181 Baseline Hemoglobin as an independent marker for survival outcome in squamous cell carcinoma of head and neck- An institutional review from tertiary cancer centre

181 Baseline Hemoglobin as an independent marker for survival outcome in squamous cell carcinoma of head and neck- An institutional review from tertiary cancer centre

Managing recurrent/advanced oropharyngeal/oesophageal cancer with cetuximab-based regimens: A case series

Background: Several clinical trials in a setting of recurrent/metastatic (R/M) squamous cell carcinoma of head and neck (HNSCC) have reported the use of cetuximab with chemotherapy (CT) or radiation therapy (RT). Methods: We report on 14 R/M HNSCC (oropharyngeal/oesophageal cancer). These are the patients who are receiving cetuximab as part of their treatment plan and are on follow-up at time of writing. Results: Seven patients were diagnosed with tongue cancer (#1, #5, #9, #10, #11, #12, and #13) and five patients with cancer of the oral cavity (patient #2, #3, #4, #7 and #14). One patient each had cancer of the oesophagus and larynx, respectively. All patients were treated with CTX (dose: 400 mg–800 mg) for R/M cancer. Patients #1, #3, #4, #5 #7 and #8 received concurrent CT (cisplatin) and RT. Patient #10 received RT and CTX. Patient #8 received docetaxel [doceAqualip], cisplatin, CTX (TPEx) as a second line of therapy after treatment failure with concomitant CT and RT for primary cancer. Patient #11 was switched to nivolumab after stabilizing on TPEx. Patient #13 received docetaxel- cisplatin-5-fluorouracil (5-FU), nivolumab, and afatinib before CTX. Conclusions: Patients had completed a minimum of one and a maximum of six cycles of TPEx. All patients are alive at time of writing.

Impact of pretreatment body mass index on the survival of head and neck cancer patients.

Differences in pretreatment body mass index (BMI) have been associated with survival in squamous cell carcinoma of head and neck (SCCHN). We examined effects of BMI on survival in SCCHN patients after stratifying patients by tumor human papillomavirus (HPV) status and subsite. Totally 2204 SCCHN patients in a prospective study were included in this secondary analysis. Multivariable Cox models were used to evaluate associations between pretreatment BMI and overall survival, disease-specific survival, and disease-free survival. BMI was significantly higher among patients with HPV-positive tumors than HPV-negative tumors. BMI >25 kg/m2 was associated with improved survival, while BMI <18.5 kg/m2 was associated with reduced survival, particularly in patients with HPV-positive oropharyngeal cancer tumors. This exploratory analysis suggests that pretreatment BMI could be an independent prognostic factor of survival outcomes in SCCHN patients, particularly in patients with HPV-positive oropharyngeal cancer tumors. Further prospective investigations are warranted.

A pan-cancer analysis of TTC9A expression level and its correlation with prognosis and immune microenvironment

To investigate the expression level of tetratricopeptide repeat protein 9A in tumors and its association with the patients' prognosis and immune infiltration. TTC9A expression in different tumor tissues and its association with prognosis, DNA methylation, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed based on data from TCGA and GTEx. TIMER and xCell were used to analyze the relationship between TTC9A expression and immune infiltration. Western blotting and RT-qPCR were used to detect the expression of TTC9A in 4 types of cancer cell lines. TTC9A expressions were significantly increased in many tumors and down-regulated in a few cancer types (P < 0.05). Western blotting and RT-qPCR showed that TTC9A expressions were elevated in lung, colon and liver cancer cells but decreased in bladder cancer cells. In head and neck squamous cell carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, low-grade glioma, malignant mesothelioma, and endometrial carcinoma tumors, a high expression of TTC9A was strongly correlated with better overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) (P < 0.05), but was correlated with worse OS, DSS, and PFI in lung adenocarcinoma, pancreatic adenocarcinoma, adrenal carcinoma, and rectal adenocarcinoma (P < 0.05). TTC9A hypermethylation was associated with a more favorable prognosis of glioblastoma multiforme, low- grade glioma, uveal melanoma, and ovarian plasmacytoid cystadenocarcinoma (P < 0.05) but with poor prognosis of squamous cell carcinoma of the uterine cervix and intracervical adenocarcinoma, squamous cell carcinoma of head and neck, squamous cell carcinoma of the lungs, adrenal carcinoma, and endometrial carcinoma (P < 0.05). In most of the cancer types, TTC9A was significantly correlated with the level of immune cell infiltration (P < 0.05). TTC9A can be used as a prognostic marker for a variety of cancers and is strongly associated with TBM, MSI and immune cell infiltration.